Page 95 - Small Animal Internal Medicine, 6th Edition

CHAPTER 3 Management of Heart Failure 67

tenth of the patient’s prior furosemide dose) has been However, marked hypokalemia or other electrolyte distur-
useful in dogs with refractory CHF and diuretic resistance. bance, severe azotemia, and dehydration can occur when
VetBooks.ir It produces greater Na excretion, has a longer half-life, used in combination with other diuretics, with excessive use,
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or in anorectic patients. Thiazides can cause hyperglycemia
and also has some anti-aldosterone effect. Adverse effects
are similar to those of furosemide but potentially more
proinsulin to insulin. Chlorothiazide’s effects begin within 1
intense. in diabetic or prediabetic animals by inhibiting conversion of
hour, peak at 4 hours, and last 6 to 12 hours. Hydrochloro-
Spironolactone thiazide produces diuresis within 2 hours, with peak effect
Spironolactone is probably more useful for its anti- at 4 hours, and duration of about 12 hours. Dosing every
aldosterone effects in cardiac and other tissues than for its other day or even less frequently (instead of q12-24h) may be
diuretic effect, although it may be a helpful adjunct in necessary to avoid serious azotemia and electrolyte abnor-
patients with chronic refractory heart failure. Spironolactone malities when used in the management of chronic refractory
is a competitive antagonist of aldosterone. In the kidney, it heart failure.
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promotes Na loss and K retention in the distal renal tubule
and can reduce the renal potassium wasting of furosemide
and other diuretics, especially when circulating aldosterone ANGIOTENSIN-CONVERTING
concentration is high. However, it has negligible diuretic ENZYME INHIBITORS
effect in normal dogs. ACEIs are indicated for most causes of chronic heart failure
Despite initial decline in aldosterone release with ACEI (see Table 3.3). Their use has led to clinical improvement and
therapy, aldosterone levels can increase with time (so-called lowered mortality rates in people with heart failure. Similar
aldosterone escape). This may involve reduced hepatic clear- benefits seem to occur in dogs with stages C and D heart
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ance, increased release stimulated by K elevation or Na failure from myocardial failure or volume overload. Cats
depletion, and local tissue aldosterone production. Spirono- with diastolic dysfunction are also thought to benefit from
lactone’s anti-aldosterone effect is thought to mitigate ACEIs. Although ACEI therapy does not delay CHF onset in
aldosterone-induced cardiovascular remodeling and barore- most dogs with preclinical (stage B) chronic MR, it remains
ceptor dysfunction. The drug has improved survival in an integral part of standard therapy once CHF develops
people with moderate to severe CHF. This might relate to a (stage C).
reduction in susceptibility to ventricular tachyarrhythmias ACEIs moderate excess NH responses in several ways;
from lessened myocardial fibrosis and inflammatory cyto- therefore they have considerable advantages over hydrala-
kine expression. In dogs with DCM and chronic MR, spi- zine and other arteriolar dilators. ACEIs have only modest
ronolactone (at 2 mg/kg/day PO) was associated with diuretic and vasodilatory effects; their main benefits arise
improved morbidity and mortality, although not all reports from opposing the effects of NH activation and abnormal
note a survival benefit. cardiovascular remodeling changes. By blocking the forma-
Spironolactone’s onset of action is slow; peak effect occurs tion of angiotensin II, ACEIs allow arteriolar and venous
within 2 to 3 days. Administration with food increases its vasodilation. The secondary inhibition of aldosterone
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bioavailability. Because it is a potassium-sparing diuretic, it release helps reduce Na and water retention and therefore
must be used cautiously in patients receiving an ACEI or edema/effusions, as well as the adverse effects of aldosterone
potassium supplement, and it is absolutely contraindicated directly on the heart. ACEIs reduce ventricular arrhyth-
in hyperkalemic patients. Adverse effects usually relate to mias and the rate of sudden death in people (and prob-
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excess K retention and GI disturbances. Spironolactone may ably animals) with heart failure, likely because angiotensin
decrease digoxin clearance. Ulcerative facial dermatitis has II–induced facilitation of norepinephrine and epineph-
occurred in cats, especially at higher doses. rine release is inhibited. Their vasodilating effects may be
Eplerenone is another aldosterone antagonist with more enhanced by vasodilator kinins normally degraded by ACE.
selective action. In experimental heart failure, eplerenone A local vasodilating effect may occur through inhibition
significantly reduced ventricular remodeling and fibrosis. of ACE found within vascular walls, even in the absence
Clinical experience in dogs and cats is lacking, however, and of high circulating renin concentrations. Local ACE inhi-
it is unclear whether this drug is more advantageous than bition may be beneficial by modulating vascular smooth
spironolactone. muscle and myocardial remodeling. However, it is unclear
whether ACE inhibitors prevent ventricular remodeling
Thiazide Diuretics and dilation in dogs with spontaneous heart disease. ACE
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Thiazide diuretics decrease Na and Cl absorption and inhibitors have been variably effective in treating dogs with
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increase Ca absorption in the distal convoluted tubules. hypertension.
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Mild to moderate diuresis with excretion of Na , Cl , K , Most ACEIs (except captopril and lisinopril) are pro-
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and Mg results, and alkalosis can occur. The thiazides drugs that are converted to their active form in the liver;
decrease renal blood flow and should not be used in azo- therefore severe liver dysfunction can interfere with this
temic animals. Adverse effects are uncommon when used conversion. Adverse effects of ACEIs include vomiting/
alone (not advised for CHF) in the absence of azotemia. diarrhea, deterioration of renal function, hypotension, and